The mechanisms of binding and entry of varicella zoster virus (VZV) into cells are unknown. We are investigating the binding of VZV to cell membrane preparations from a variety of cultured cell-lines, to isolated proteins, glycoconjugates and to synthetic peptides. Inhibition of VZV infectivity in diploid human lung cells is being used to asses potential receptor-mimicking molecules for ability to block VZV binding and infection of cells. Monoclonal and polyclonal antibodies to cell membrane proteins are being developed to identify the specific cell surface molecules that serve as receptors for VZV. We found that heparin inhibited infectivity of VZV, in contrast another glycosaminoglycan, chondroitin sulfate did not inhibit VZV infectivity. VZV binding to cell membrane preparations was inhibited by added heparin suggesting that an important mechanism of interaction of VZV with cells involves heparin. Several assays were developed to measure binding of VZV and of herpesvirus glycoproteins to immobilized heparin. VZV was found to bind to immobilized heparin. Soluble VZV gB (gpII) has been produced using the vaccinia-T7 expression system to investigte glycoprotein to heparin receptor binding using ELISA based and biosensor technologies. The interaction of glycoprotein B of herpes simplex virus type 2 (HSV-2) with heparin-like glycosaminoglycans is being investigated using the biosensor technique. This study will lead to a detailed understanding of the affinity and specificity of the HSV gB to heparin interaction and serves as a model system to explore inhibitor compounds that may be used to interupt the interaction of herpesviruses with their cellular receptors and therefore act as antiviral drugs.